1. Field of the Invention
Steroids play a significant biological role in the animal and vegetable kingdom in being a mediator in many biological processes. In addition, the steroids, because of their hormonal activity, have been a basis for the production of a wide variety of synthetic drugs, which differ in various structural ways from naturally occuring steroids and either mimic steroidal activities or provide new biological activity.
Because of the many inherent synthetic difficulties in modifying naturally occurring steroids and the uncertainties involved in depending upon sufficient supplies of naturally occurring steroids, particularly plant steroids, there has been increasing interest in providing synthetic routes to steroid products. Any synthesis of a steroid is complicated by the perhydrocyclopentanophenanthrene structure and the particular geometry of the structure as to the ring fusions. In addition, the presence of bridgehead alkyl groups at C-10 and C-13 add additional complications. There is a further consideration of substituents which are frequently present at C-3 and C-17. Finally, there is the need that in each of the steps, particularly the latter steps, the desired geometry is retained and good yield of the desired products is obtained without the presence of only difficultly removable contaminants.
2. Description of the Prior Art
Johnson, Accounts of Chemical Research, 1968, discloses a wide variety of nonenzymic biogenetic-like olefinic cyclizations of polyunsaturated compounds using various groups which serve as sources of carbocations. Johnson, et al., J. Amer. Chem. Soc., 92, 4461 (1970) discloses the synthesis of polyenes which may be cyclized to a homosteroid having a 6 -membered D ring. Johnson, et al., ibid, 93, 4330 (1971) discloses an acetylenic terminating group in the formation of bi and tricyclic compounds. Johnson, et al., ibid, 93, 4332 (1971) shows the formation of progesterone employing an intermediate having an acetylenic terminating group. Markezich, et al., ibid, 95, 4414 (1973) shows a cyclization to a pregnone structure employing a cyclohexenyl initiating ring and an acetylenic terminating group. McCarry, et al., ibid, 95, 4416 (1973) discloses cyclization of a polyenine compound to a pregnone structure which is then modified to progesterone. Use of nitroalkane to capture the vinyl carbonium ion which is formed at the acetylenic terminating group is described in Morton, et al., ibid, 95, 4417 (1973). Polyenines employing cyclohexenol as initiators is described in Carney, et al., ibid, 96, 2549 (1974). Use of an acetal as an initiating group is found in Johnson, et al., ibid, 96, 3979 (1974).